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珊瑚蛇Micrurus tener tener毒液在C57BL/6小鼠中诱导的促炎反应和止血障碍。

Pro-inflammatory response and hemostatic disorder induced by venom of the coral snake Micrurus tener tener IN C57BL/6 mice.

作者信息

Salazar Emelyn, Salazar Ana Maria, Taylor Peter, Ibarra Carlos, Rodríguez-Acosta Alexis, Sánchez Elda, Pérez Karin, Brito Beatriz, Guerrero Belsy

机构信息

Laboratorio de Fisiopatología, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.

Laboratorio de Patología Celular y Molecular, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.

出版信息

Toxicon. 2018 Aug;150:212-219. doi: 10.1016/j.toxicon.2018.06.063. Epub 2018 Jun 8.

Abstract

Micrurus venoms are known to induce mainly neurotoxicity in victims. However, other manifestations, including hemorrhage, edema, myotoxicity, complement activation, and hemostatic activity have been reported. In order to develop a more complete pharmacological profile of these venoms, inflammatory responses and hemostasis were evaluated in C57BL/6 mice treated with a sub-lethal dose of M. t. tener (Mtt) venom (8 μg/mouse), inoculated intraperitoneally. The venom induced moderate bleeding into the abdominal cavity and lungs, as well as infiltration of leukocytes into the liver. After 30 min, the release of pro-inflammatory mediators (TNF-α, IL-6, and NO) were observed, being most evident at 4 h. There was a decrease in hemoglobin and hematocrit levels at 72 h, a prolongation in coagulation times (PT and aPTT), a decrease in the fibrinogen concentration and an increase in fibrinolytic activity. In this animal model, it was proposed that Mtt venom induces inflammation with the release of mediators such as TNF-α, in response to the toxins. These mediators may activate hemostatic mechanisms, producing systemic fibrinolysis and hemorrhage. These findings suggest alternative treatments in Micrurus envenomations in which neurotoxic manifestations do not predominate.

摘要

已知珊瑚蛇毒液主要会在受害者身上诱发神经毒性。然而,也有其他表现的报道,包括出血、水肿、肌毒性、补体激活和止血活性。为了更全面地了解这些毒液的药理特性,对腹腔注射亚致死剂量(8μg/小鼠)的细斑珊瑚蛇(Micrurus tener, Mtt)毒液的C57BL/6小鼠的炎症反应和止血情况进行了评估。该毒液导致腹腔和肺部出现中度出血,以及白细胞浸润肝脏。30分钟后,观察到促炎介质(TNF-α、IL-6和NO)的释放,在4小时时最为明显。72小时时血红蛋白和血细胞比容水平下降,凝血时间(PT和aPTT)延长,纤维蛋白原浓度降低,纤维蛋白溶解活性增加。在这个动物模型中,研究表明细斑珊瑚蛇毒液会因毒素刺激而释放TNF-α等介质,从而诱发炎症。这些介质可能激活止血机制,导致全身纤维蛋白溶解和出血。这些发现为神经毒性表现不占主导的珊瑚蛇中毒提供了替代治疗方法。

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